Is TLR3 p.Pro298= (c.894A>T) pathogenic?

TLR3 p.Pro298= (c.894A>T) is classified Likely benign in TLR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-09). Very rare (popmax 0.000424%, nfe); Associated with herpes simplex encephalitis, susceptibility to, 1.

What condition is associated with TLR3 p.Pro298= (c.894A>T)?

TLR3 p.Pro298= (c.894A>T) is associated with herpes simplex encephalitis, susceptibility to, 1 (ClinVar).

How common is TLR3 p.Pro298= (c.894A>T) in the general population?

TLR3 p.Pro298= (c.894A>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

TLR3 p.Pro298=

c.894A>T · rs1471779820 · VCV2759215

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

herpes simplex encephalitis, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -3.8
Overall
CADD	0.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,024 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,166 alleles · very rare exomes 5/1,461,872 · genomes 0/152,294 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TLR3
Protein: p.Pro298=
Coding: c.894A>T
MANE Select: NM_003265
dbSNP: rs1471779820
Type: single nucleotide variant
Location: chr4:186082580 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 20 PDB

Full TLR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

herpes simplex encephalitis, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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TLR3 p.Ala549Thr Uncertain significance ★★ ⚠ same condition
TLR3 p.Ala795Val Uncertain significance ★★ ⚠ same condition
TLR3 p.Ala839Asp Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg331Gln Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg331Trp Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg809Lys Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg885Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tlr3-p-pro298 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown